Measurement device

Abstract

The present invention provides a measurement device in which a measurement chip having a reaction region for detecting a test substance is used, and the reaction of a test substance in the reaction region is measured utilizing fluorescence, the measurement device comprising: a measurement unit that directs excitation light on the reaction region and detects fluorescence emitted from the reaction region; an attachment unit to which the measurement chip is detachably attached; a checking chip for checking the measurement unit, the checking chip being detachably attached to the attachment unit; and a storage unit for storing the checking chip, the storage unit being provided at a location different from the attachment unit.

Description

Measuring equipment

[0001] The technology of the present disclosure relates to a measurement device.

[0002] Known measuring devices, such as the one described in JP 2014-071056 A, use a measuring chip having a reaction region for detecting a test substance and measure the reaction of the test substance in the reaction region. The measuring device described in JP 2014-071056 A measures the reaction by irradiating the reaction region with excitation light and detecting fluorescence excited by the excitation light.

[0003] The measurement device described in JP 2014-071056 A is provided with a calibration area for optically calibrating a measurement unit including a light source that irradiates excitation light and a detection unit that detects fluorescence. When the calibration area is provided outside the measurement chip, it is provided on the side of the mounting unit to which the measurement chip is mounted. When the calibration area is provided inside the measurement chip, it is provided on the side of the reaction area of ​​the measurement chip.

[0004] As a method for checking the measurement unit, such as calibrating the measurement unit, as described in JP 2014-071056 A, a dedicated check chip that is detachable from the attachment part and is separate from the measurement chip is being considered. The use of such a check chip has the following advantages over the method described in JP 2014-071056 A:

[0005] First, there is less concern about the device configuration becoming complicated compared to the method of providing a check area such as the calibration area described in JP 2014-071056 A in a measurement device that is external to the measurement chip. In other words, because the check area can be provided in the check chip rather than in the measurement device, there is no need to significantly change the irradiation position of the excitation light from the time of measurement when checking the measurement unit, and there is less concern about the device configuration becoming complicated.

[0006] Another advantage is that, compared to the method of providing a check area inside the measuring chip, the cost of the measuring chip can be suppressed because, while providing a check area on every measuring chip would increase the cost of the measuring chip, if a checking chip is prepared, there is no need to provide a check area on the measuring chip.

[0007] However, when a check chip dedicated to checking is prepared separately from the measurement chip in this way, there is a concern that another problem may arise in that the check chip may be lost while not in use.

[0008] One embodiment of the technique of the present disclosure provides a measuring device in which there is little concern about losing a check tip even when a check tip is used to check a measuring unit.

[0009] In order to achieve the above-mentioned object, the measuring device according to the technology of the present disclosure is a measuring device that uses a measuring chip having a reaction region for detecting the test substance and measures the reaction of the test substance in the reaction region by utilizing fluorescence, and is equipped with a measuring unit that irradiates the reaction region with excitation light and detects the fluorescence emitted from the reaction region, an attachment unit to which the measuring chip is detachably attached, a checking chip for checking the measuring unit that is detachably attached to the attachment unit, and a storage unit that stores the checking chip that is provided in a location separate from the attachment unit.

[0010] The check chip has a check area for optically checking the measurement part, and it is preferable that the position of the check area when the check chip is attached to the attachment part is the same as the position of the reaction area when the measurement chip is attached to the attachment part.

[0011] The checking chip preferably has a checking area that emits fluorescence when irradiated with excitation light.

[0012] The housing that houses the measuring unit and the attachment unit is provided with an opening / closing mechanism that can open and close an opening formed in the housing, and the storage unit is preferably located inside the housing in a position that allows the check chip stored in the storage unit to be removed when the opening / closing mechanism is opened.

[0013] The opening is preferably a maintenance opening provided for maintenance purposes.

[0014] The maintenance opening is preferably a maintenance opening for the measurement unit.

[0015] It is preferable that the opening and closing mechanism be a maintenance door that opens and closes the maintenance opening, and that the storage section be provided inside the maintenance door.

[0016] Within the housing, the storage section is preferably provided in a location where the temperature difference between the storage section and the environment in which the measurement section is placed is within 10°C.

[0017] The temperature difference is preferably within 5°C.

[0018] Preferably, the reaction is measured using surface plasmon resonance.

[0019] According to the technology of the present disclosure, even when a check tip is used to check the measuring unit, there is little concern about the check tip being lost.

[0020] 1 is an external view of a measuring device of the present disclosure; FIG. 2 is a block diagram showing an outline of the internal configuration of the measuring device; FIG. 3 is a schematic diagram showing an example of an analysis chip used in the measuring device; FIG. 4 is a schematic diagram showing how a sample is extracted from a sample container by a sample processing unit using a nozzle tip; FIG. 5 is a schematic diagram showing how a sample in a nozzle tip is injected into a reagent cell and stirred by a sample processing unit; FIG. 6 is a diagram showing the positional relationship between a flow path and a measurement unit, and a method for moving the measurement unit; FIG. 7 is a diagram explaining an overview of fluorescence detection using a measurement unit; FIG. 8 is a diagram showing the angle of incidence of excitation light and the degree of plasmon enhancement; FIG. 9 is a diagram showing the configuration of a checking chip; FIG. 10 is a diagram showing the positional relationship between a check region of a checking chip and a measurement object; FIG. 11 is a diagram showing an overview of a check process using a checking chip; FIG. 12 is a diagram showing the positional relationship between a storage unit and a measurement unit;

[0021] The measuring device 100 shown in FIG. 1 is, for example, a measuring device that measures an antigen-antibody reaction of a test substance A (see FIGS. 4 and 5, etc.) contained in a specimen collected from a living body in order to perform immunodiagnosis. The measuring device 100 is, for example, a measuring device that uses a fluorometry method. The fluorometry method measures the antigen-antibody reaction of the test substance A by irradiating excitation light onto a fluorescent label F (see FIGS. 5 and 7, etc.) bound to the test substance A and detecting the fluorescence emitted from the fluorescent label F. More specifically, the measuring device 100 measures the antigen-antibody reaction of the test substance A by enhancing the fluorescence emitted by the fluorescent label F using the surface plasmon resonance phenomenon. This type of measuring method is called surface plasmon field-enhanced fluorescence spectroscopy (SPFS), for example.

[0022] As shown in FIG. 1, when performing a measurement using the measurement device 100, a sample container CB containing a sample, a nozzle chip NC used to extract the sample and reagent, and an analytical chip 10 formed with a reagent cell and a microchannel are set in the measurement device 100. Note that the sample container CB, nozzle chip NC, and analytical chip 10 are all disposable and discarded after a single use. The measurement device 100 then injects the sample into the channel 15 (see FIG. 3, etc.) of the analytical chip 10, and, as an example, performs a quantitative measurement of analyte A in the sample. The analytical chip 10 is an example of a "measurement chip" according to the technology of the present disclosure. The analytical chip 10 is also referred to as an analytical cartridge or a measurement cartridge.

[0023] The specimen is, for example, blood, more specifically, serum, plasma, or whole blood. The specimen may be other than blood, and may be urine, nasal fluid, saliva, feces, body cavity fluid, or the like. The test substance A contained in the specimen may be, for example, a nucleic acid, a protein, an amino acid, a carbohydrate, a lipid, or a modified molecule or complex thereof. The complex may be, for example, a tumor marker, a signal transduction substance, or a hormone.

[0024] The top surface of the housing 102 of the measuring device 100 is provided with an opening 103 that is opened when mounting the analytical chip 10 and an operation panel including an operation unit 51 and a display unit 52. At the back of the opening 103 is provided a mounting unit 101 for mounting the analytical chip 10. The mounting unit 101 is provided with a main mounting unit 101A for mounting the analytical chip 10, and sub-mounting units 101B for mounting the sample container CB and the nozzle chip NC, respectively. The analytical chip 10 is detachably mounted on the main mounting unit 101A. The sample container CB and the nozzle chip NC are similarly detachably mounted on the sub-mounting unit 101B.

[0025] The cover 104 is a cover that opens and closes the opening 103. As shown in Fig. 1, when the cover 104 is opened, the mounting portion 101 is exposed from the opening 103, and an analytical chip 10 or the like can be mounted. When performing a measurement, the cover 104 is closed.

[0026] In FIG. 2 , which schematically shows the internal configuration of the measuring device 100, the measuring device 100 includes a mounting unit 101, as well as a sample processing unit 20, a measurement unit 30, a control unit 40, and the like. The mounting unit 101 moves between a mounting position and a measurement position within the measuring device 100 (see also FIG. 13 ). The mounting position is a position corresponding to the opening 103, and is the position where the analytical chip 10 and the like are mounted. The measurement position is the position where the measurement unit 30 is located, and is the position where measurement is performed on the analytical chip 10. As an example, the mounting position is located closer to the front in the depth direction of the housing 102, and the measurement position is located further back than the mounting position. The mounting unit moving mechanism 34 moves the mounting unit 101 between the mounting position and the measurement position.

[0027] As shown in Figure 1, in addition to the analysis chip 10, a nozzle chip NC and a specimen container CB are attached to the mounting section 101, so that when the mounting section 101 moves to the measurement position, the nozzle chip NC and specimen container CB are also transported to the measurement position.

[0028] The sample processing unit 20 extracts a sample from a sample container CB (see FIG. 4, etc.) using a nozzle chip NC, mixes and stirs the extracted sample with a reagent, and generates a sample solution SL (see FIG. 5, etc.). The sample processing unit 20 also injects the generated sample solution SL into the analysis chip 10.

[0029] Specifically, the sample processing unit 20 includes a nozzle movement mechanism 21 and a pump 22. The nozzle movement mechanism 21 is a mechanism for moving the nozzle 24 up and down and left and right. The pump 22 is connected to the nozzle 24 via piping 26 and ejects and aspirates liquid such as a sample using gas. A single-use nozzle tip NC is attached to the tip of the nozzle 24. The nozzle tip NC is replaced for each sample, and the used nozzle tip NC is discarded. This prevents contamination between different samples. The sample processing unit 20 obtains the nozzle tip NC from the mounting unit 101 located at the measurement position. The sample processing unit 20 also accesses the sample container CB and analysis chip 10 mounted in the mounting unit 101 via the nozzle movement mechanism 21.

[0030] The measurement unit 30 measures the reaction of the test substance A contained in the specimen solution SL injected into the analysis chip 10 by a fluorescence method utilizing surface plasmon resonance. The measurement unit 30 includes an excitation light irradiation unit 31, an incident angle adjustment mechanism 33, a fluorescence detection unit 32, etc.

[0031] The excitation light irradiating unit 31 irradiates the analysis chip 10 with excitation light Le (see FIG. 7). The excitation light irradiating unit 31 is composed of, for example, an LD (Laser Diode) which is a light emitting unit that emits the excitation light Le, and a reflecting mirror that reflects the excitation light Le. The incident angle adjusting mechanism 33 adjusts the incident angle of the excitation light Le irradiated onto the analysis chip 10. The fluorescence detecting unit 32 detects fluorescence Lf (see FIG. 7) emitted from the fluorescent label F excited by the excitation light Le in the analysis chip 10, and outputs a fluorescence detection signal to the control unit 40. The fluorescence detecting unit 32 is composed of, for example, a photodiode, a photomultiplier, a CCD (Charge Coupled Device) image sensor, a CMOS (Complementary Metal Oxide Semiconductor Image Sensor) image sensor, etc.

[0032] The measurement unit moving mechanism 36 is a moving mechanism that moves the measurement unit 30. As will be described later, the analytical chip 10 is provided with a plurality of regions to be measured, and the measurement unit moving mechanism 36 moves the measurement unit 30 relative to the analytical chip 10 so that the plurality of regions of the analytical chip 10 can be measured.

[0033] The control unit 40 comprehensively controls each unit of the measuring device 100. An operation unit 51 and a display unit 52 are connected to the control unit 40. The control unit 40 also has a built-in timer (not shown) that performs various timing operations. The operation unit 51 is composed of buttons, a cross key, etc., and is used to input operation instructions, such as a measurement start instruction, to the control unit 40. Patient information related to the sample is also input through the operation unit 51. The display unit 52 is composed of, for example, a liquid crystal panel, and displays measurement results, status indicating the operating state, warnings, and other messages.

[0034] The control unit 40 controls the sample processing unit 20 in accordance with a measurement start instruction from the operation unit 51 to inject the sample solution SL into the analysis chip 10. Then, it operates the measurement unit moving mechanism 36 and the measurement unit 30 to perform the measurement. During the measurement, the control unit 40 outputs, as a measurement result, the concentration of the test substance A, for example, based on the fluorescence detection signal obtained from the fluorescence detection unit 32. Note that in addition to the concentration of the test substance A, data analysis may be performed based on the concentration, and the analysis results may be included in the measurement results and output. The control unit 40 outputs the measurement results to the display unit 52.

[0035] The control unit 40 includes, for example, a central processing unit (CPU) 40A and a memory 40B. The control unit 40 is also communicatively connected to a data storage (not shown). As is well known, the CPU 40A executes a program loaded into the memory 40B to perform processing defined by the program. The memory 40B includes a random access memory (RAM) and a read-only memory (ROM). The data storage may be a hard disk drive (HDD) or a solid state drive (SSD), etc.

[0036] FIG. 3 is a schematic diagram showing an example of an analytical chip 10. The analytical chip 10 has a structure in which an inlet 12, an outlet 13, reagent cells 14A and 14B, and a flow path 15 are formed in a main body 11 made of a dielectric material such as an optically transparent resin. The inlet 12 is connected to the outlet 13 via the flow path 15. A sample solution SL is injected through the inlet 12 and supplied to the flow path 15. The reagent cells 14A and 14B are containers that contain a fluorescent reagent to be mixed with the sample in the sample container CB. The fluorescent reagent performs pretreatment, such as adsorbing to proteins in the sample to dissociate the target, for example, for pH adjustment. The openings of the reagent cells 14A and 14B are sealed with a sealing member that is pierced when the sample and fluorescent reagent are mixed.

[0037] A reaction region 16 for detecting a test substance A in a sample is provided within the flow channel 15. A test region TR, a first control region CR1, and a second control region CR2 are formed in the reaction region 16. If the side of the flow channel 15 where the injection port 12 is located is defined as the upstream side of the reaction region 16, the first control region CR1, the test region TR, and the second control region CR2 are provided in this order from the upstream side to the downstream side.

[0038] A first antibody B1 (see FIG. 7 ) is immobilized on the test region TR and captures the analyte A. The first antibody B1 is an example of an antibody that specifically reacts with the analyte A. The first control region CR1 is a region that normally does not capture anything and is a so-called negative control region in which the signal value serving as the base of the fluorescence detection signal is 0. The second control region CR2 is a region in which a substance that captures the fluorescent label F in the sample solution SL is immobilized. The second control region CR2 captures the fluorescent label F regardless of whether it is bound to the analyte A. Therefore, the second control region CR2 is a region in which the signal value serving as the base of the fluorescence detection signal is a value corresponding to the concentration of the fluorescent label F contained in the sample solution SL and is a so-called positive control region. Sample abnormalities, measurement abnormalities, etc. are detected based on the fluorescence detection signals from the first control region CR1 and the second control region CR2.

[0039] When a command to start measurement is issued, the sample processing unit 20 attaches a nozzle tip NC to the nozzle 24 and aspirates the sample from the sample container CB using the nozzle tip NC, as shown in FIG. 4 . The sample processing unit 20 then pierces the seal member of the reagent cell 14A, as shown in FIG. 5 , mixes and stirs the sample with the reagent in the reagent cell 14A, and then aspirates the sample solution SL again using the nozzle tip NC. This operation is similarly performed for the reagent cell 14B. The reagent is a second antibody B2 labeled with a fluorescent label F. The second antibody B2 specifically binds to the analyte A present in the sample. Therefore, by mixing and stirring the sample and reagent, the second antibody B2 binds to the analyte A, generating a sample solution SL in which the surface of the analyte A is modified with the second antibody B2 and the fluorescent label F.

[0040] The sample processing unit 20 then moves the nozzle tip NC containing the sample solution SL above the injection port 12. The sample processing unit 20 injects the sample solution SL into the injection port 12 from above the injection port 12 by discharging the nozzle 24. This causes a pool of the sample solution SL to form inside the injection port 12. The sample processing unit 20 then removes the nozzle tip NC from the nozzle 24, inserts the tip of the nozzle 24 into the outlet 13, and performs a suction operation in this state. This causes the sample solution SL pooled inside the injection port 12 to be supplied to the flow channel 15. The sample solution SL supplied to the flow channel 15 flows downstream within the flow channel 15 and comes into contact with the reaction region 16.

[0041] 6 is an explanatory diagram showing the first control region CR1, test region TR, and second control region CR2 of the analytical chip 10, and the movement of the measurement unit 30 relative to the analytical chip 10. The first control region CR1, test region TR, and second control region CR2 are arranged along the flow direction (X direction) of the sample solution SL in the flow channel 15. The main body 11 is provided with a prism 11A having an incident surface onto which the excitation light Le is incident, corresponding to each of the first control region CR1, test region TR, and second control region CR2.

[0042] In the measurement unit 30, the excitation light irradiation unit 31 is disposed at a position facing the incident surface of the prism 11A of the analytical chip 10 mounted on the mounting unit 101 at the measurement position. On the other hand, the fluorescence detection unit 32 is disposed above the flow path 15 of the analytical chip 10 at a position facing the first control region CR1, the test region TR, and the second control region CR2, and is disposed at a position where it can detect fluorescence from each region.

[0043] The measurement unit moving mechanism 36 (see FIG. 2) linearly moves the excitation light irradiation unit 31 and the fluorescence detection unit 32 in the flow direction (X direction) of the flow channel 15, i.e., along the arrangement direction of the first control region CR1, the test region TR, and the second control region CR2. This enables the measurement unit 30 to selectively move to a position facing each of the first control region CR1, the test region TR, and the second control region CR2, and measure the reaction in each region.

[0044] 7 is an explanatory diagram showing the relationship between the reaction region 16 of the analysis chip 10, the excitation light irradiation unit 31, and the fluorescence detection unit 32, as viewed from the X direction. Note that while the description in FIG. 7 focuses on the test region TR, the same applies to the first control region CR1 and the second control region CR2.

[0045] The main body 11 of the analysis chip 10 has a dielectric plate 17. The front surface 17A of the dielectric plate 17 forms the bottom surface of the flow channel 15, and a prism 11A is provided on the back surface 17B. A metal film 18 that forms the test region TR, the first control region CR1, and the second control region CR2 is formed on the dielectric plate 17. In this example, the material of the metal film 18 is gold. The dielectric plate 17 and the prism 11A are molded integrally, and the prism 11A is also a dielectric.

[0046] In the dielectric plate 17, the front surface 17A corresponds to the main surface that contacts the back surface of the metal film 18, which is opposite to the surface on which the test region TR is provided.

[0047] As described above, the first antibody B1 is immobilized on the metal film 18 of the test region TR, and the first antibody B1 captures the test substance A modified with the fluorescent label F and the second antibody B2 using a so-called sandwich method. As described above, the first control region CR1 is a negative control region, and, as an example, no antibody is immobilized on the metal film 18 of the first control region CR1. In other words, the first control region CR1 is simply the metal film 18. Also, as described above, the second control region CR2 is a positive control region, and a substance that captures the fluorescent label F is immobilized on the metal film 18 of the second control region CR2, regardless of the presence or absence of the test substance A.

[0048] The excitation light irradiation unit 31 applies excitation light Le to the surface 17A of the dielectric plate 17, which is the front surface that contacts the back surface of the metal film 18, via the prism 11A. The incident angle θ of the optical axis with respect to the surface 17A is equal to or greater than the critical angle that satisfies the total reflection condition. This allows the excitation light Le to be applied to the back surface of the metal film 18 in the test region TR, the first control region CR1, and the second control region CR2. As described above, the excitation light irradiation unit 31 is provided with a reflecting mirror. The reflecting mirror is rotatable, and the excitation light irradiation unit 31 can change the incident angle θ of the excitation light Le by rotating the reflecting mirror. The incident angle adjustment mechanism 33 adjusts the incident angle of the excitation light Le without changing the irradiation position of the excitation light Le on the back surface of the metal film 18 by rotating the reflecting mirror, for example, by using a lens.

[0049] When excitation light Le is incident on the back surface of the metal film 18 by the excitation light irradiation unit 31 at a specific incident angle equal to or greater than the critical angle, evanescent waves Ew seep out onto the metal film 18, and these evanescent waves Ew excite surface plasmons on the surface of the metal film 18. These surface plasmons generate an electric field distribution on the surface of the metal film 18, forming an electric field enhanced region. Then, the fluorescent label F bound to the first antibody B1 fixed on the metal film 18 is excited by the evanescent waves Ew and emits enhanced fluorescence Lf. The fluorescence detection unit 32 receives the enhanced fluorescence Lf and outputs a fluorescence detection signal corresponding to the amount of received fluorescence Lf.

[0050] Here, the specific incident angle θ at which surface plasmon resonance occurs and the enhanced fluorescence Lf reaches a maximum is called the resonance angle. The resonance angle varies depending on factors such as the type of specimen solution SL that contacts the surface of the metal film 18. Therefore, the incident angle θ of the excitation light Le is adjusted by the incident angle adjustment mechanism 33.

[0051] FIG. 8 shows the relationship between the plasmon enhancement of the fluorescence Lf and the reflectance of the reflected light RL of the excitation light Le versus the angle of incidence θ when plasma is used as the sample. The profile in FIG. 8 is an example where the wavelength of the excitation light Le is 658 nm, the thickness of the metal film 18 is 36 nm, the material of the metal film 18 is gold, and the material of the prism 11A is PMMA (polymethyl methacrylate). Here, the plasmon enhancement is an index that indicates how many times the amount of enhanced fluorescence Lf is compared to the reference value, where the amount of fluorescence Lf without enhancement is taken as the reference value. Because the plasmon enhancement is proportional to the amount of fluorescence Lf detected by the fluorescence detection unit 32, the relationship between the amount of fluorescence Lf and the angle of incidence θ in FIG. 8 will be the same even if the vertical axis represents the amount of fluorescence Lf.

[0052] In Fig. 8 , the incident angle θ at which the plasmon enhancement of the fluorescence Lf reaches a peak value and becomes a local maximum is identified as the resonance angle. In the example shown in Fig. 8 , the resonance angle is 73.6 degrees. Because the excitation light Le consumes energy in plasmon enhancement, the reflected light RL of the excitation light Le is significantly attenuated near the resonance angle, in contrast to the plasmon enhancement of the fluorescence Lf, and the reflectance becomes a local minimum. By adjusting the incident angle, the resonance angle at which the plasmon enhancement of the fluorescence Lf becomes a local maximum, as shown in Fig. 8 , can be identified.

[0053] As shown in FIG. 9 , the measuring device 100 includes a check chip 200 specifically designed for checking the measuring unit 30. One example of a check of the measuring unit 30 is an optical check of the measuring unit 30. Specifically, the check checks whether the fluorescence detection unit 32 is outputting an appropriate fluorescence detection signal corresponding to the amount of received fluorescence Lf, or whether the amount of excitation light Le emitted by the excitation light irradiator 31 is within a predetermined appropriate range. Based on the results of these checks, an abnormality or malfunction of the measuring unit 30 is determined. Furthermore, the amount of light emitted by the excitation light irradiator 31 may decrease due to deterioration over time of the measuring unit 30. In such cases, calibration may be performed, such as determining whether the amount of excitation light Le emitted by the measuring unit 30 is within an appropriate range based on the check results and adjusting the amount of light emitted. The check chip 200 is also referred to as a check cartridge.

[0054] The check chip 200 has almost the same external shape and size as the analytical chip 10, and is detachable from the mounting part 101 in the same manner as the analytical chip 10. The check chip 200 is used when an abnormality or malfunction of the measurement part 30 is suspected, or when performing periodic maintenance of the measurement part 30. When checking the measurement part 30, the check chip 200 is mounted on the mounting part 101.

[0055] The checking chip 200 has a check region 202 for performing an optical check within its main body 201. The check region 202 is an area that emits test fluorescence Lf_test (see FIG. 11 ) having substantially the same wavelength as the fluorescence Lf when exposed to excitation light Le emitted by the excitation light irradiation unit 31. The check region 202 corresponds to the reaction region 16 of the analytical chip 10, and its external shape and size are substantially similar to those of the reaction region 16. The position of the check region 202 in the main body 201 of the checking chip 200 is also the same as that of the reaction region 16 in the main body 11 of the analytical chip 10. Therefore, the position of the check region 202 when the checking chip 200 is mounted on the mounting unit 101 is the same as the position of the reaction region 16 when the analytical chip 10 is mounted on the mounting unit 101.

[0056] As a result, as shown in Figures 10 and 11, when the mounting part 101 is in the measurement position, the relative positional relationship between the measurement part 30 and the check area 202 is the same as the relative positional relationship between the measurement part 30 and the reaction area 16 shown in Figures 6 and 7.

[0057] The check area 202 has a long, narrow strip shape, similar to the reaction area 16. The check area 202 is divided into three sections in the longitudinal direction by three apertures 201A (see FIG. 9 ) provided in the main body 201. In the check area 202, the areas divided by the three apertures 201A correspond to a first control area CR1, a test area TR, and a second control area CR2.

[0058] 10, the check area 202 is configured by, for example, a transparent plate 203 made of resin or glass containing a fluorescent substance. When the surface of the transparent plate 203 facing the fluorescence detection unit 32 is defined as the front surface, a prism 204 similar to the prism 11A of the analysis chip 10 is provided on the opposite back surface.

[0059] As shown in Fig. 11 , excitation light Le from the excitation light irradiation unit 31 passes through a prism 204 and enters a transparent plate 203 that constitutes the check area 202. The incident excitation light Le excites the fluorescent material in the check area 202, causing the fluorescent material to emit test fluorescence Lf_test. The test fluorescence Lf_test enters the fluorescence detection unit 32, which outputs a fluorescence detection signal that corresponds to the amount of test fluorescence Lf_test received. Because the check area 202 is constituted by the transparent plate 203, excitation light Le can be irradiated from the back surface of the transparent plate 203, and test fluorescence Lf_test can be emitted toward the fluorescence detection unit 32 that is arranged on the front surface side of the transparent plate 203, as in the measurement shown in Fig. 7 .

[0060] Each aperture 201A regulates the amount of emitted test fluorescence Lf_test so that the amount of light received by the fluorescence detection unit 32 is approximately the same when the excitation light irradiation unit 31 irradiates the same excitation light Le at each position in the X direction of the measurement unit 30 (see Figure 10).

[0061] In this example, as with the analysis chip 10, a prism 204 is provided on the check chip 200, but the prism 204 may not be necessary if the configuration is such that excitation light Le is irradiated onto the check area 202 and test fluorescence Lf_test is emitted.

[0062] At each position in the X direction of the measurement unit 30 (see FIG. 10 ), the amount of received test fluorescence Lf_test relative to the amount of emitted excitation light Le is determined by the specifications (such as the type and content of the fluorescent material) of the check area 202. This correspondence between the amount of emitted light and the amount of received light is stored in advance in the memory 40B of the control unit 40, etc.

[0063] When checking the measurement unit 30, the measurement device 100 irradiates the check area 202 with a preset light emission amount of excitation light Le and compares the amount of test fluorescence Lf_test received by the fluorescence detection unit 32 at that time with the correspondence stored in memory 40B. Based on the comparison result, the measurement device 100 determines whether there is an abnormality or malfunction in the measurement unit 30 as described above and outputs a check result including the determination result. The measurement device 100 also outputs the amount of received light as a check result in accordance with the fluorescence detection signal from the fluorescence detection unit 32. Based on these check results, the user can determine whether the light emission amount of the excitation light Le is within an appropriate range and perform optical calibration, such as adjusting the light emission amount of the excitation light Le.

[0064] 9, the checking chip 200 is provided with, in addition to the optical check region 202, an insertion port 206 into which a nozzle chip NC is inserted to check the operation of the sample processing unit 20. The insertion port 206 is provided in the main body 201 at a position corresponding to the inlet 12 and outlet 13 of the analytical chip 10. The measuring device 100 checks the operation of the pump 22 and the like of the sample processing unit 20 by causing the sample processing unit 20 to discharge and aspirate test liquid using the insertion port 206.

[0065] 12 , a maintenance opening 207 is formed on the side of the housing 102 of the measuring device 100. The maintenance opening 207 is an opening for performing maintenance such as cleaning of the measuring unit 30 or the nozzle 24. A maintenance door 208 is provided as an opening / closing mechanism that can open and close the maintenance opening 207. When performing maintenance, the maintenance door 208 is opened.

[0066] The outer surface of the maintenance door 208 forms part of the side surface of the housing 102. A storage section 209 for storing the check chip 200 is provided on the inner surface of the maintenance door 208 facing the inside of the housing 102. The storage section 209 functions as a storage location for keeping the check chip 200 while the check chip 200 is not in use. The storage section 209 is, for example, box-shaped with an open top. Of course, a lid may be provided on the opening at the top.

[0067] The storage section 209 is provided in a location separate from the mounting section 101, and is an example of a "storage section" according to the technology of the present disclosure. The inside of the maintenance door 208 is inside the housing 102, and is a position from which the check chip 200 stored in the storage section 209 can be removed when the maintenance door 208, which is an opening / closing mechanism, is opened. This position is an example of a "removable position" according to the technology of the present disclosure.

[0068] As shown in FIG. 13 , the maintenance opening 207 is an opening for performing maintenance on the measurement unit 30. Therefore, the distance between the maintenance opening 207 and the measurement unit 30 is such that the state of the measurement unit 30 can be visually confirmed from the maintenance opening 207, or such that a hand inserted through the maintenance opening 207 can reach the measurement unit 30. In this example, at least a portion of the maintenance opening 207 is positioned so as to overlap with the measurement unit 30 in the depth direction from the front to the rear of the housing 102. In this example, the storage unit 209 is provided on the inner surface of the maintenance door 208 that opens and closes the maintenance opening 207. Therefore, when the maintenance door 208 is closed, the storage unit 209 is located to the side of the measurement unit 30 in the width direction perpendicular to the depth direction of the housing 102. Therefore, the environmental temperatures of the storage unit 209 and the measurement unit 30 within the housing 102 are approximately the same.

[0069] 14, the fluorescent material used in the check region 202 of the check chip 200 has a temperature-dependent light emission amount, i.e., the light emission amount decreases as the temperature increases. The light emission amount of the test fluorescence Lf_test in the check region 202 serves as reference information when optically checking the measurement unit 30. Therefore, if the light emission amount of the test fluorescence Lf_test changes depending on the temperature condition of the storage environment of the check chip 200, the reliability of the check results of the measurement unit 30 may not be ensured.

[0070] In this example, the storage unit 209 is provided inside the housing 102 of the measuring device 100. Therefore, the environment in which the check chip 200 is stored when not in use experiences less temperature change than when the check chip 200 is provided outside the housing 102. Therefore, the amount of light emitted by the test fluorescence Lf_test in the check area 202 is stable, improving the reliability of the check by the measuring unit 30.

[0071] Furthermore, when performing a check, the check chip 200 is attached to the attachment portion 101 and used at a measurement position where the measurement unit 30 is located. In order to ensure stability in the amount of light emitted by the test fluorescence Lf_test during a check, it is preferable that there is little change in the environmental temperature between the storage environment and the usage environment. In the measurement device 100, there is little change in the environmental temperature between the storage portion 209 where the check chip 200 is stored when not in use and the measurement position where the check chip 200 is placed when in use. In this way, the check chip 200 is stored at a temperature substantially the same as the usage environment even when not in use, so the amount of light emitted by the test fluorescence Lf_test during a check is stable. This improves the reliability of the check by the measurement unit 30.

[0072] Inside the housing 102, the storage unit 209 is preferably provided in a location where the temperature difference between the environment in which the measurement unit 30 is provided is within 10°C. More preferably, the temperature difference is within 5°C. In this example, the temperatures of the environment in which the storage unit 209 is provided and the environment in which the measurement unit 30 is provided are approximately the same, satisfying the requirement that the temperature difference be within 5°C.

[0073] The operation of the above configuration will now be described. In the measuring device 100, the check chip 200 is stored in a storage section 209 provided on the inner surface of the maintenance door 208 when it is not being used to check the measuring unit 30. When an abnormality or malfunction is suspected in the measuring device 100, or during regular maintenance, the measuring unit 30 is checked using the check chip 200.

[0074] For example, the user opens the maintenance door 208, looks into the inside of the housing 102 through the maintenance opening 207, checks for abnormalities in the external shape of the measuring unit 30, and also performs a check using the check chip 200. Because the check chip 200 is stored in a storage unit 209 provided on the inner surface of the maintenance door 208, there is little concern about it being lost, and the user can easily find the check chip 200.

[0075] The user attaches the check chip 200 to the attachment unit 101, which is in the attachment position, and instructs the measuring device 100 to perform a check process. As shown in FIGS. 2 and 13, the measuring device 100 moves the attachment unit 101 from the attachment position to the measurement position. Then, as shown in FIGS. 10 and 11, the measuring device 100 irradiates the check area 202 of the check chip 200 with excitation light Le from the excitation light irradiating unit 31. When the check area 202 is irradiated with the excitation light Le, the fluorescent material in the check area 202 is excited and emits test fluorescence Lf_test. The fluorescence detecting unit 32 receives the test fluorescence Lf_test and outputs a detection signal according to the amount of light received.

[0076] The control unit 40 outputs the check result to the display unit 52 or the like based on the detection signal. If the amount of received light is previously within the appropriate range, the control unit 40 outputs a check result indicating that there is no abnormality or malfunction in the measurement unit 30 during the check process using the check chip 200. If the amount of received light is not within the appropriate range, the control unit 40 outputs a check result indicating the possibility of an abnormality or malfunction. If such a check result is output, a decrease in the output of the excitation light irradiation unit 31 or a malfunction of the fluorescence detection unit 32 is suspected. In this case, the user calibrates the measurement unit 30 by adjusting the output of the excitation light irradiation unit 31 or, if possible, adjusting the gain of the detection signal from the fluorescence detection unit 32. If the malfunction or abnormality is not resolved even after calibration, the user requests repair, such as replacement of the measurement unit 30. Of course, such checks may also be performed by a technician performing maintenance on the measurement device 100 instead of the user.

[0077] As described above, the measuring device 100 according to the technique of the present disclosure comprises a check chip 200 for checking the measuring unit 30, the check chip 200 being detachably attached to the attachment unit 101, and a storage unit 209 for storing the check chip 200, the storage unit 209 being provided in a location separate from the attachment unit 101. Therefore, even when the check chip 200 for checking the measuring unit 30 is used, there is little concern about the check chip 200 being lost.

[0078] Furthermore, the checking chip 200 has a checking area 202 for optically checking the measurement unit 30, and the position of the checking area 202 when the checking chip 200 is mounted on the mounting unit 101 is the same as the position of the reaction area 16 when the analytical chip 10, which is an example of a measurement chip, is mounted on the mounting unit 101. Therefore, the measurement unit 30 can perform the check at the same position as when it is measured, without moving to a position different from that used during measurement.

[0079] If the position of the calibration area differs from the position of the reaction area, as in the case of the calibration area (corresponding to the check area 202) described in JP 2014-071056 A, the movement range of the measurement unit 30 will differ between measurement and checking, raising concerns that the movement mechanism of the measurement unit 30 will become complicated. In contrast, in the measurement device 100 of the present disclosure, the relative positional relationship between the check area 202 and the measurement unit 30 during checking is the same as the relative positional relationship between the reaction area 16 and the measurement unit 30 during measurement, so there is little concern that the movement mechanism of the measurement unit 30 will become complicated.

[0080] The check chip 200 has a check area 202 that emits test fluorescence Lf_test as fluorescence when irradiated with excitation light Le. This allows checking of both the excitation light irradiator 31 and the fluorescence detector 32. For example, if the check area uses a reflecting mirror and an excitation light detector, it is possible to check only the output of the excitation light irradiator 31. Compared to such a configuration, the check area 202 can reduce the complexity of the device configuration for checking.

[0081] Furthermore, in the measuring device 100, the housing 102 that houses the measuring unit 30 and the attachment unit 101 is provided with a maintenance door 208 (an example of an opening / closing mechanism) that can open and close a maintenance opening 207 (an example of an opening) formed in the housing 102, and the storage unit 209 is provided inside the housing 102 at a position that allows the check chip 200 stored in the storage unit 209 to be removed when the maintenance door 208 is opened. If the storage unit 209 is provided inside the housing 102, there is less concern about the check chip 200 being lost compared to when the storage unit 209 is provided outside the housing 102.

[0082] In this example, the storage unit 209 is provided inside the housing 102, but the storage unit 209 may also be provided, for example, on the outer surface of the housing 102. Of course, if the check chip 200 that is used less frequently is provided outside the housing 102, it may not be convenient to use during normal use, so it is preferable that the storage unit 209 is provided inside the housing 102 as in the above example.

[0083] Furthermore, the storage section 209 is located in a position where the check chip 200 can be removed when an opening / closing mechanism such as the maintenance door 208 is opened, making it easy to remove the check chip 200 stored inside the housing 102 and making it easy to use.

[0084] Furthermore, the opening that is opened and closed by an opening / closing mechanism (for example, a maintenance door 208) and through which the check chip 200 can be removed is a maintenance opening 207 provided for maintenance purposes. The maintenance opening 207 is opened and closed during maintenance, which is the timing when the check chip 200 is used, and therefore makes it easy to find the check chip 200.

[0085] The maintenance opening 207 is an opening for maintenance of the measuring unit 30. The check chip 200 is used to check the measuring unit 30. Therefore, it is easier to use than when the opening through which the check chip 200 can be removed is an opening for maintenance of something other than the measuring unit 30.

[0086] The opening and closing mechanism is a maintenance door 208 that opens and closes the maintenance opening 207, and the storage section 209 is provided inside the maintenance door 208. Therefore, as described above, the check chip 200 can be easily found during maintenance.

[0087] 13, the environments in which the storage unit 209 and the measurement unit 30 are placed in the measurement device 100 are substantially the same. Therefore, the temperature difference is also substantially the same. The location of the storage unit 209 is an example of a location where the temperature difference from the environment in which the measurement unit 30 is placed is within 10°C, and is also an example of a location where the temperature difference is within 5°C.

[0088] Even if the light emission intensity of the test fluorescence Lf_test of the checking chip 200 has temperature dependency as shown in FIG. 14, if the temperature difference is within 10°C, the change in the light emission intensity between storage and use of the checking chip 200 can be suppressed within a practical range. This ensures the reliability of the check results. More preferably, the temperature difference is within 5°C. In this example, since these temperature conditions are met, the reliability of the check results can be ensured. The location of the storage unit 209 is not limited to this example, but it is preferable to select a location where the temperature difference is as small as possible.

[0089] Furthermore, the measuring device 100 measures the reaction using surface plasmon resonance. In the cases shown in Figures 7 and 8, when surface plasmon resonance is used, it is necessary to identify the resonance angle at which the fluorescence Lf is enhanced based on the detection signal of the fluorescence Lf, so calibration of the measuring unit 30 is extremely important. Therefore, the technology of the present disclosure related to the checking chip 200 that checks the measuring unit 30 is particularly effective.

[0090] In the above embodiment, the maintenance door 208 is exemplified as an opening / closing mechanism for the opening through which the check chip 200 can be removed. However, something other than the maintenance door 208 may be used. For example, a disposal box 210 as shown in FIG. 15 may be used. The disposal box 210 is, for example, a box that stores single-use nozzle chips NC. The disposal box 210 is attached to a box mounting opening 211, which is an example of an opening used in the housing 102, so as to be able to be removed. A storage section for the check chip 200 may be provided in the disposal box 210, or the disposal box 210 itself may be used as a storage section. In other words, the box mounting opening 211 is an example of an opening through which the check chip 200 can be removed, and the disposal box 210 is an example of an opening / closing mechanism for the box mounting opening 211.

[0091] In addition to these, the storage section may be provided near an opening for the check chip 200 provided in the housing 102. The opening / closing mechanism may be of any type as long as it can close an opening. It may be a door type that rotates on a hinge, like the maintenance door 208 shown in the example above, or a door type that opens and closes by sliding. It may also be a removable lid type, or a drawer type like the disposal box 210.

[0092] Furthermore, in the above embodiment, the case where the test substance A is an antigen has been described as an example, but the test substance A may also be an antibody.

[0093] Furthermore, in the above embodiment, a measurement device that utilizes surface plasmon resonance has been described as an example, but the present invention can also be applied to a measurement device that does not utilize surface plasmon resonance, as long as the measurement device utilizes fluorescence excited by irradiation with excitation light.

[0094] Furthermore, the technologies described in the following supplementary items can be understood from the above description. [Supplementary Item 1] A measuring device that uses a measurement chip having a reaction area for detecting a test substance and measures the reaction of the test substance in the reaction area by utilizing fluorescence, the measuring device comprising: a measurement unit that irradiates the reaction area with excitation light and detects fluorescence emitted from the reaction area; an attachment unit to which the measurement chip is detachably attached; a check chip for checking the measurement unit, the check chip being detachably attached to the attachment unit; and a storage unit that stores the check chip, the storage unit being provided in a location separate from the attachment unit. [Supplementary Item 2] The measuring device described in Supplementary Item 1, wherein the check chip has a check area for optically checking the measurement unit, and the position of the check area when the check chip is attached to the attachment unit is the same as the position of the reaction area when the measurement chip is attached to the attachment unit. [Supplementary Item 3] The measuring device described in Supplementary Item 1 or Supplementary Item 2, wherein the check chip has a check area that emits fluorescence when irradiated with excitation light. [Supplementary Item 4] The measuring device according to any one of Supplementary Items 1 to 3, wherein the housing that houses the measuring unit and the attachment unit is provided with an opening / closing mechanism that can open and close an opening formed in the housing, and the storage unit is provided inside the housing at a position that allows the check chip stored in the storage unit to be removed when the opening / closing mechanism is opened. [Supplementary Item 5] The measuring device according to Supplementary Item 4, wherein the opening is a maintenance opening provided for maintenance. [Supplementary Item 6] The measuring device according to Supplementary Item 5, wherein the maintenance opening is a maintenance opening for the measuring unit. [Supplementary Item 7] The measuring device according to Supplementary Item 6, wherein the opening / closing mechanism is a maintenance door that opens and closes the maintenance opening, and the storage unit is provided inside the maintenance door. [Supplementary Item 8] The measuring device according to Supplementary Item 4, wherein the storage unit is provided inside the housing at a location that is within a temperature difference of 10°C from the environment in which the measuring unit is placed. [Supplementary Item 9] The measuring device according to Supplementary Item 8, wherein the temperature difference is within 5°C.[Supplementary Item 10] The measuring device according to any one of Supplementary Items 1 to 9, which measures a reaction using surface plasmon resonance.

[0095] The above describes preferred embodiments of the present disclosure, but the present disclosure is not limited to the above embodiments, and it goes without saying that various configurations can be adopted, such as combinations of the embodiments and modified examples, as long as they do not deviate from the gist of the present disclosure.

[0096] Furthermore, in the above embodiment, for example, the hardware structure of a processor that executes various processes, such as the control unit 40, can be any of the various processors listed below. The various processors include a CPU, which is a general-purpose processor that executes software (programs) and functions as various processing units, as well as dedicated electrical circuits, such as a PLD (Programmable Logic Device) whose circuit configuration can be changed after manufacture, such as an FPGA (Field-Programmable Gate Array), and an ASIC (Application Specific Integrated Circuit), which is a processor with a circuit configuration designed specifically for executing specific processes.

[0097] The various processes described above may be executed by one of these various processors, or may be executed by a combination of two or more processors of the same or different types (for example, a combination of multiple FPGAs, or a combination of a CPU and an FPGA). Furthermore, multiple processing units may be configured by a single processor. An example of configuring multiple processing units by a single processor is a system-on-chip (SOC), in which a processor is used to realize the functions of an entire system including multiple processing units on a single IC (Integrated Circuit) chip.

[0098] In this way, the various processing units are configured as hardware structures using one or more of the various processors described above.

[0099] Furthermore, more specifically, the hardware structure of these various processors can be an electric circuit that combines circuit elements such as semiconductor elements.

[0100] In addition to the operating program of the measuring device 100, the technology of the present disclosure also extends to a computer-readable storage medium (such as a USB memory or a DVD (Digital Versatile Disc)-ROM (Read Only Memory)) that non-temporarily stores the operating program of the measuring device 100.

[0101] The above-described description and illustrations are a detailed explanation of the parts related to the technology of the present disclosure and are merely an example of the technology of the present disclosure. For example, the above description of the configuration, functions, actions, and effects is an explanation of an example of the configuration, functions, actions, and effects of the parts related to the technology of the present disclosure. Therefore, it goes without saying that unnecessary parts may be deleted, new elements may be added, or replacements may be made to the above-described description and illustrations within the scope of the gist of the technology of the present disclosure. Furthermore, to avoid confusion and facilitate understanding of the parts related to the technology of the present disclosure, the above-described description and illustrations omit explanations of common technical knowledge that do not require particular explanation to enable the implementation of the technology of the present disclosure.

[0102] In this specification, "A and / or B" is synonymous with "at least one of A and B." In other words, "A and / or B" means that it may be only A, only B, or a combination of A and B. Furthermore, in this specification, the same concept as "A and / or B" is also applied when three or more things are expressed by connecting them with "and / or."

[0103] The disclosure of Japanese Patent Application No. 2023-140446, filed on August 30, 2023, is incorporated herein by reference in its entirety. In addition, all documents, patent applications, and technical standards described herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. A measuring device that uses a measuring chip having a reaction area for detecting a test substance and measures the reaction of the test substance in the reaction area by utilizing fluorescence, comprising: a measuring unit that irradiates the reaction area with excitation light and detects the fluorescence emitted from the reaction area; an attachment unit to which the measuring chip is detachably attached; a checking chip for checking the measuring unit, which is detachably attached to the attachment unit; and a storage unit that stores the checking chip, which is provided in a location separate from the attachment unit.

2. The measuring device according to claim 1, wherein the checking chip has a checking area for optically checking the measuring section, and the position of the checking area when the checking chip is attached to the attachment section is the same as the position of the reaction area when the measuring chip is attached to the attachment section.

3. The measuring device according to claim 1, wherein the checking chip has a checking area that emits fluorescence when irradiated with excitation light.

4. The measuring device according to claim 1, wherein a housing that houses the measuring unit and the mounting unit is provided with an opening / closing mechanism capable of opening and closing an opening formed in the housing, and the storage unit is provided inside the housing at a position where a check chip stored in the storage unit can be removed when the opening / closing mechanism is opened.

5. The measuring device according to claim 4, wherein the opening is a maintenance opening provided for maintenance purposes.

6. The measuring device according to claim 5, wherein the maintenance opening is a maintenance opening for the measuring section.

7. The measuring device according to claim 6, wherein the opening / closing mechanism is a maintenance door that opens and closes the maintenance opening, and the storage section is provided inside the maintenance door.

8. The measuring device according to claim 4, wherein the storage section is provided inside the housing at a location within a temperature range of 10° C. that differs from the environment in which the measuring section is placed.

9. The measuring device according to claim 8, wherein the temperature difference is within 5°C.

10. The measuring device according to claim 1, wherein the reaction is measured using surface plasmon resonance.

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